TEM8 marks neovasculogenic tumor-initiating cells in triple-negative breast cancer.
Enhanced neovasculogenesis, especially vasculogenic mimicry (VM), contributes to the development of triple-negative breast cancer (TNBC). Breast tumor-initiating cells (BTICs) are involved in forming VM; however, the specific VM-forming BTIC population and the regulatory mechanisms remain undefined. We find that tumor endothelial marker 8 (TEM8) is abundantly expressed in TNBC and ... serves as a marker for VM-forming BTICs. Mechanistically, TEM8 increases active RhoC level and induces ROCK1-mediated phosphorylation of SMAD5, in a cascade essential for promoting stemness and VM capacity of breast cancer cells. ASB10, an estrogen receptor ER? trans-activated E3 ligase, ubiquitylates TEM8 for degradation, and its deficiency in TNBC resulted in a high homeostatic level of TEM8. In this work, we identify TEM8 as a functional marker for VM-forming BTICs in TNBC, providing a target for the development of effective therapies against TNBC targeting both BTIC self-renewal and neovasculogenesis simultaneously.
Mesh Terms:
Animals, Antineoplastic Agents, Biomarkers, Tumor, Breast, Carcinogenesis, Cell Line, Tumor, Cell Self Renewal, Female, Humans, Mastectomy, Mice, Microfilament Proteins, Middle Aged, Neoplastic Stem Cells, Neovascularization, Pathologic, Receptors, Cell Surface, Triple Negative Breast Neoplasms, Xenograft Model Antitumor Assays
Animals, Antineoplastic Agents, Biomarkers, Tumor, Breast, Carcinogenesis, Cell Line, Tumor, Cell Self Renewal, Female, Humans, Mastectomy, Mice, Microfilament Proteins, Middle Aged, Neoplastic Stem Cells, Neovascularization, Pathologic, Receptors, Cell Surface, Triple Negative Breast Neoplasms, Xenograft Model Antitumor Assays
Nat Commun
Date: Dec. 20, 2020
PubMed ID: 34285210
View in: Pubmed Google Scholar
Download Curated Data For This Publication
233475
Switch View:
- Interactions 36